Equine Conjugated Estrogens and Medroxyprogesterone Acetate (Premphase) is an estrogen and progestin combination tablet that is used for the prevention of postmenopausal osteoporosis, vasomotor symptoms, and vaginal atrophy.

Equine conjugated estrogens and medroxyprogesterone acetate Uses:

• Osteoporosis prevention (female):

  • It is indicated for the prevention of osteoporosis in postmenopausal women
  • Limitations of use: Should be used only where a significantly higher risk of postmenopausal osteoporosis.

• Vasomotor symptoms associated with menopause:

  • In instances when the vasomotor symptoms of menopause are mild to severe, it is advised for therapy.

• Vulvar and vaginal atrophy associated with menopause:

  • It is used to treat menopausal-related atrophy of the vulva and vagina.
    Use should be restricted to topical vaginal treatments if just treating vulva and vaginal atrophy.

Note:

The term "genitourinary syndrome of menopause" (GSM) has been approved as a new word for vulvovaginal atrophy by both the North American Menopause Society and the International Society for the Study of Women's Sexual Health. All genital and urinary signs and symptoms brought on by a decline in estrogen due to menopause are included in GSM.

• Guideline recommendations: When progesterone is required, micronized progesterone is preferable over medroxyprogesterone acetate due to safety concerns.

Equine conjugated estrogens and medroxyprogesterone acetate Dose in Adults

Equine Conjugated Estrogens and Medroxyprogesterone Acetate General dosing considerations in females:

• As part of individual-based therapy for treatment objectives, risk factors, and general health, recurrent evaluation should be done for the optimal dose, duration, and mode of administration when used as hormone replacement therapy after menopause.
• For postmenopausal women with uteruses, combined estrogen/progestin treatment is recommended to lower the risk of endometrial cancer.
• In general, people who have undergone hysterectomies do not require progestin; however, if endometriosis has a history, one can be required.
• When progesterone is required, micronized progesterone is preferable over medroxyprogesterone acetate due to safety concerns.

Equine Conjugated Estrogens and Medroxyprogesterone Acetate Dose in adults:

• Use as an alternative agent in the treatment of Osteoporosis prevention, vasomotor symptoms associated with menopause, or vulvar and vaginal atrophy associated with menopause:

• Premphase:

  • Oral: One maroon conjugated estrogen 0.625 mg tablet a day on days 1 through 14 and 1 light blue conjugated estrogen 0.625 mg/MPA 5 mg tablet daily on days 15 through 28

• Prempro:

  • Oral: One conjugated estrogen/MPA tablet once a day
  • Maximum dose: 1 conjugated estrogen 0.625 mg/MPA 5 mg tablet a day

Note: Menopausal <2 years with an intact uterus can benefit from a cyclic regimen (continuous regimens may be associated with unscheduled bleeding).

Use in Children:

Not indicated.

Pregnancy Risk Category: X

• Contraindicated during pregnancy
• When taken in combination with estrogen and progestin, they have no teratogenic effect.

Use during breastfeeding:

• Breast milk contains progesterone and estrogens.
• Estrogens reduce the quality and quantity of human milk.
• Manufacturer recommendation: Lactating women should be cautious

Dose in Kidney disease:

The manufacturer has not provided any dose adjustment in the labeling

Dose in Liver disease:

Contraindicated with hepatic dysfunction/ liver disease.

Common Side Effects of Equine Conjugated Estrogens and Medroxyprogesterone Acetate (Premphase):

• Gastrointestinal:

  • Abdominal pain

• Central nervous system:

  • Headache

• Genitourinary:

  • Mastalgia
  • Dysmenorrhea

Less Common Side Effects of Equine Conjugated Estrogens and Medroxyprogesterone Acetate (Premphase):

• Gastrointestinal:

  • Diarrhea
  • Constipation
  • Nausea
  • Flatulence
  • Increased Appetite
  • Eructation

• Cardiovascular:

  • Edema
  • Vasodilatation
  • Chest Pain
  • Peripheral Edema
  • Hypertension
  • Palpitations

• Dermatologic:

  • Pruritus
  • Skin Rash
  • Skin Discoloration
  • Diaphoresis
  • Acne Vulgaris
  • Alopecia
  • Xeroderma

• Central Nervous System:

  • Depression
  • Dizziness
  • Migraine
  • Pain
  • Emotional Lability
  • Nervousness
  • Anxiety
  • Hypertonia
  • Insomnia

• Endocrine & Metabolic:

  • Weight Gain
  • Decreased Glucose Tolerance
  • Hypermenorrhea

• Genitourinary:

  • Vaginal Hemorrhage
  • Vaginitis
  • Breakthrough Bleeding
  • Uterine Spasm
  • Leukorrhea
  • Breast Hypertrophy
  • Pelvic Pain
  • Vulvovaginal Candidiasis
  • Cervical Changes
  • Abnormal Pap Smear
  • Breast Engorgement
  • Urinary Incontinence

• Hematologic & Oncologic:

  • Malignant Neoplasm Of Breast

• Neuromuscular & Skeletal:

  • Weakness
  • Back Pain
  • Leg Cramps

• Infection:

  • Candidiasis
  • Infection

• Respiratory:

  • Pharyngitis
  • Sinusitis
  • Flu-Like Symptoms

Contraindications to Equine Conjugated Estrogens and Medroxyprogesterone Acetate (Premphase):

• Angioedema, anaphylactic reaction to estrogen or medroxyprogesterone or any component of formulation
• Atypical genital bleeding that is not diagnosed
• DVT or PE (current and/or historical of)
• Arterial thromboembolic Disease e.g. stroke, MI
• Breast cancer (known or suspected)
• A known or suspected estrogen-dependent tumor
• Hepatic impairment and disease
• Antithrombin deficiencies, known protein C, and antithrombin deficiencies, as well as other thrombophilic conditions, are all known.
• Pregnancy.

There is not much evidence of cross-reactivity between estrogens and progestins. Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Anaphylaxis

  • Anaphylaxis can happen at any stage of therapy. Emergency medical services may be required.
  • Reports of angioedema that can affect the tongue, face, feet, larynx and hands have been made.

• Breast cancer: [US Boxed Warn]

  • The women health initiative (WHI) has shown that there is an increased chance of breast cancer in women who use MPA acetate and CE. The increased risk of invasive cancer with CE after hysterectomy was not increased by using CE alone.
  • As therapy is stopped, the risk of developing an infection decreases.
  • The type and dosage of estrogen/progestin, timing of therapy initiation, duration, route of administration and patient characteristics all impact the risk.
  • An abnormal mammogram may indicate an increase in breast density. This should be referred for further treatment with estrogen alone or with combination progestin therapy.
  • Patients with breast cancer and bone metastasis may experience severe hypercalcemia. If this happens, discontinue estrogen.

• Dementia: [US Boxed Warning]

  • The Women's Health Initiative Memory Study, (WHIMS) found that women aged >=65 years old who were taking Conjugate estrogen either alone or in combination was more likely to develop dementia.
  • As the WHI study was conducted on patients >=65, this effect was not observed in younger postmenopausal females.
  • For dementia, hormone therapy is not recommended.

• Endometrial Cancer: [US Boxed Warn]

  • Endometrial cancer is more likely in women who have unopposed estrogen. The addition of progestin (reduces endometrial hyperplasia), can reduce this risk.
  • If the patient experiences abnormal vaginal bleeding postmenopausal, it is important to have proper testing and endometrial sampling done.
  • It is not possible to compare the risks of natural estrogens and synthetic estrogens.
  • Risk increases with increasing estrogen doses and lengths. The greatest risk is for use over 5 years. This risk may continue after therapy has been discontinued.

• Endometriosis:

  • Estrogens can exacerbate endometriosis. Patients who have had hysterectomy may experience malignant transformation of their residual endometrium if they are not given estrogen therapy.
  • Women with endometrium after hysterectomy need to be given progestin.

• The Lipid Effects

  • Estrogen compounds increase HDL-cholesterol, decreased LDL-cholesterol, increases triglycerides with prior hypertriglyceridemia;
  • If you have pancreatitis, discontinue use.

• Ovarian cancer:

  • Rarely has there been an increase in the risk of ovarian carcinoma after postmenopausal estrogen therapy or estrogen/progestin therapy.

• Retinal vascular embolism:

  • Estrogen can cause retinal vein thrombosis
  • If the patient experiences vision loss, proptosis or migraine, discontinue immediately. If the patient is suffering from papilledema, retinal vascular lesion or other symptoms, discontinue use immediately.

• Asthma

  • Asthma can be exacerbated by using caution.

• Carbohydrate intolerance:

  • This may cause impaired glucose tolerance.
  • Before starting treatment for diabetics, patients should consider their age, metabolic and cardiovascular risk factors.

• Cardiovascular disease: [US-Boxed Warning]

  • Women's Health Initiative (WHI), studies show that Conjugate Estrogen has a higher risk of stroke and deep vein thrombosis in women aged 50-79. There is also an increased risk for myocardial injury (PE) and pulmonary emboli (MI) in these women.
  • If the patient has other significant cardiovascular risk factors, such as DM, prior VTE, SLE or obesity, discontinue treatment. Take control of the risk factors
  • Transdermal administration has lower risk of thrombotic event and may be preferred to treat vasomotor symptoms during menopause for patients at high risk for cardiovascular disease.
  • Contraindicated in active DVT, PE and arterial thromboembolic diseases (stroke and MI), as well as a history of such conditions.

• Fluid retention can lead to more severe diseases

  • If the patient has fluid retention, such as cardiac dysfunction or renal dysfunction, be cautious.

• Epilepsy:

  • Be cautious with epilepsy. It may cause exacerbation.

• Gallbladder disease

  • Gallbladder disease can be increased by excessive estrogen, especially if used postmenopausally.

• Hepatic dysfunction

  • Estrogens can alter metabolism and cause hepatic dysfunction.
  • Be cautious if you have a history of cholestatic jaundice, especially if it is associated with pregnancy or estrogen use.
  • If the patient has jaundice, hepatic impairment, or develops jaundice, discontinue treatment
  • Contraindicated for hepatic impairment

• Hepatic hemomangiomas

  • Be cautious with hepatic hemomangiomas. This could lead to exacerbation

• Hereditary angioedema:

  • Exogenous estrogens may be used to exacerbate angioedema.

• Hypoparathyroidism:

  • Hypoparathyroidism should be treated with caution as estrogen-induced hypocalcemia may occur.

• Migraine

  • Migraine can be severe so use caution.

• Porphyria

  • Patients with porphyria should be treated cautiously. This could lead to exacerbation.

• SLE:

  • SLE should be used with caution. Exacerbations could occur

Equine conjugated estrogens and medroxyprogesterone acetate: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Before therapy, baseline risk for breast cancer and Cerebrovascular disease.
• During therapy, breast, and pelvic examination;
• Blood pressure;
• Unscheduled bleeding lasting >6 months for endometrial pathology (sooner in patients who are obese, diabetic, or have a history of endometrial cancer);
• Serum triglycerides (2 weeks after starting therapy in patients with baseline level >200 mg/dL);
• TSH (6 - 12 weeks after starting oral therapy in patients taking thyroid replacement)

Menopausal symptoms:

• Efficacy beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate. Duration of treatment should be evaluated at least annually.

Note: FSH and serum estradiol monitoring is not useful when managing vasomotor symptoms or GSM. Prevention of osteoporosis:

• Bone density measurement

How to administer Equine Conjugated Estrogens and Medroxyprogesterone Acetate (Premphase)?

Administer at the same time each day.

Mechanism of action of Equine Conjugated Estrogens and Medroxyprogesterone Acetate (Premphase):

See individual agents (Equine Conjugated Estrogens and Medroxyprogesterone Acetate)

International Brand Names of Equine conjugated estrogens and medroxyprogesterone acetate:

• Premphase
• Prempro
• Premplus
• Climatrol HT Ciclico
• Climatrol HT Continuo
• Climopax
• Climopax Cyclo
• Novafac
• Novafac 30
• Novafac CC
• Novofac CC
• Plentiva
• Plentiva Cycle
• Premelle
• Premelle Ciclico
• Premelle Continuo
• Premelle Cycle
• Premelle Cycle 5
• Premelle LD
• Premelle Lite
• Premelle Right
• Premia
• Premia Continuous
• Premique
• Prempro Monofascio
• Repogen Conti
• Selecta

Equine conjugated estrogens and medroxyprogesterone acetate Brand Names in Pakistan:

No Brands Available in Pakistan.